In utero estrogenic exposures and transgenerational risk for breast cancer

子宫内雌激素暴露和乳腺癌的跨代风险

基本信息

  • 批准号:
    8043496
  • 负责人:
  • 金额:
    $ 7.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-04-01 至 2013-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): In utero estrogenic exposures and transgenerational risk for breast cancer Background: Research in humans and animals suggests that what an expecting mother eats or is exposed to during pregnancy, can affect her offspring's susceptibility to disease in adulthood. Using a rat model, we have previously shown that a maternal diet high in fat during pregnancy is associated with increase in pregnancy estrogen levels and breast cancer risk in daughters. More recently, it was shown that what an expecting mother is exposed to during pregnancy affects risk of certain diseases not only in her offspring but subsequent generations as well. These effects are thought to be inheritable through epigenetic mechanisms. Objective/ hypothesis: We propose to study whether exposing pregnant rats to a high fat diet or an estrogen- supplemented diet will affect the risk of mammary cancer in the offspring and two subsequent generations. We hypothesize that in utero estrogenic exposures will increase the risk of mammary cancer of the female offspring (F1) and will be transmitted to the subsequent generations (F2/F3) through epigenetic mechanisms. A better understanding of how the in utero environment leads to modulation of breast cancer risk in the offspring and subsequent generations could have great implications for breast cancer prevention. Specific Aims: (1) Determine whether exposure of pregnant rats to estrogens or a high-fat diet is associated with increased mammary cancer risk in the offspring (F1) and subsequent generations(F2/F3). (2) Determine whether these in utero exposures are associated with changes in mammary gland developmental biology in the offspring (F1) and subsequent generations (F2/F3). (3) Determine whether the effects of these in utero exposures are transmitted to subsequent generations through epigenetic mechanisms. Study Design: Pregnant Sprague-Dawley rats will receive a high fat diet or an estradiol supplemented diet during gestation and mammary cancer development will be monitored in the offspring (F1). To address if the phenotype seen in the offspring is passed to subsequent generations, we will mate the female and male offspring (F1) and examine mammary cancer risk in the next generation (F2). Similarly, the F2 generation will be mated and mammary cancer examined in the offspring (F3). We will examine whether the mammary cancer phenotype in the F1, F2 and F3 generations is associated with changes in epigenetic and gene expression patterns in the mammary gland, employing genome-wide methylation and microarrays studies. We will also examine the mammary gland morphology to assess changes in mammary gland development.
描述(由申请人提供): 子宫内雌激素暴露和乳腺癌的跨代风险背景:对人类和动物的研究表明,准妈妈在怀孕期间饮食或接触的食物可能会影响其后代成年后对疾病的易感性。我们之前通过大鼠模型表明,怀孕期间母亲的高脂肪饮食与怀孕期间雌激素水平的增加和女儿患乳腺癌的风险有关。最近的研究表明,准妈妈在怀孕期间所接触的环境不仅会影响其后代,还会影响后代患某些疾病的风险。这些效应被认为是通过表观遗传机制遗传的。目的/假设:我们建议研究怀孕大鼠接受高脂肪饮食或补充雌激素的饮食是否会影响后代和后续两代患乳腺癌的风险。我们假设子宫内雌激素暴露会增加女性后代(F1)患乳腺癌的风险,并通过表观遗传机制遗传给后代(F2/F3)。更好地了解子宫内环境如何导致后代和后代乳腺癌风险的调节可能对乳腺癌预防产生重大影响。具体目标: (1) 确定怀孕大鼠暴露于雌激素或高脂肪饮食是否与子代 (F1) 和后代 (F2/F3) 的乳腺癌风险增加相关。 (2) 确定这些子宫内暴露是否与后代 (F1) 和后代 (F2/F3) 的乳腺发育生物学变化有关。 (3) 确定这些子宫内暴露的影响是否通过表观遗传机制传递给后代。研究设计:怀孕的斯普拉格-道利大鼠将在妊娠期间接受高脂肪饮食或补充雌二醇的饮食,并将监测后代(F1)的乳腺癌发展情况。为了确定后代中看到的表型是否会遗传给后代,我们将雌性和雄性后代 (F1) 交配,并检查下一代 (F2) 的乳腺癌风险。同样,F2 代将进行交配,并对后代 (F3) 进行乳腺癌检查。我们将采用全基因组甲基化和微阵列研究,检查 F1、F2 和 F3 代的乳腺癌表型是否与乳腺表观遗传和基因表达模式的变化相关。我们还将检查乳腺形态以评估乳腺发育的变化。

项目成果

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Sonia de Assis其他文献

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{{ truncateString('Sonia de Assis', 18)}}的其他基金

Paternal DDT exposure and programming of metabolic dysfunction and cancer in offspring: Understanding the role of sperm mirnas and placenta development
父系 DDT 暴露以及后代代谢功能障碍和癌症的规划:了解精子 mirnas 和胎盘发育的作用
  • 批准号:
    10529335
  • 财政年份:
    2021
  • 资助金额:
    $ 7.44万
  • 项目类别:
Paternal DDT exposure and programming of metabolic dysfunction and cancer in offspring: Understanding the role of sperm mirnas and placenta development
父系 DDT 暴露以及后代代谢功能障碍和癌症的规划:了解精子 mirnas 和胎盘发育的作用
  • 批准号:
    10356857
  • 财政年份:
    2021
  • 资助金额:
    $ 7.44万
  • 项目类别:
Parental Exposure to High Fats Diets and Risk of Pancreatic Cancer in the Offspri
父母高脂肪饮食与后代患胰腺癌的风险
  • 批准号:
    9319232
  • 财政年份:
    2015
  • 资助金额:
    $ 7.44万
  • 项目类别:
In utero estrogenic exposures and transgenerational risk for breast cancer
子宫内雌激素暴露和乳腺癌的跨代风险
  • 批准号:
    7896278
  • 财政年份:
    2010
  • 资助金额:
    $ 7.44万
  • 项目类别:

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